足细胞损伤在多柔比星肾损害大鼠病程中变化及意义  

Changes and its siginificance of podocyte injury in rats with adriamycin-induced nephropathy

作　　者：沈雯雯[1] 周琪[1] 汪渊[2] 陈柯[3] 梁维龙[1] 阚春明[1] 戴宏[1] 张伯科[1] 

机构地区：[1]安徽医科大学第一附属医院肾内科,合肥230022 [2]安徽医科大学分子生物学实验室、生物化学教研室和安徽省／省部共建教育部重要遗传基因资源利用重点实验室,合肥230032 [3]安徽医科大学附属省立医院病理科,合肥230001

出　　处：《安徽医科大学学报》2009年第2期177-181,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金项目(编号:070413074)

摘　　要：目的通过检测肾组织WT-1的表达变化来动态观察多柔比星肾纤维化大鼠足细胞的数目的变化,探讨其与蛋白尿和肾纤维化发展的时效量效关系。方法36只SD大鼠随机分为模型组和对照组,尾静脉注射多柔比星建立多柔比星肾纤维化大鼠模型,首次注射多柔比星起,第4、7、10、13周每组处死模型组大鼠5只和对照组4只,留取肾脏标本,应用光镜、电镜观察肾组织的病理改变,BCA法检测24h尿蛋白排泄率,免疫组化和Western blot的半定量方法检测大鼠肾皮质中WT-1蛋白的表达。结果第4周开始,肾纤维化组大鼠蛋白尿显著高于对照组(P<0.01),肾脏病理在第7周时出现局灶肾小球硬化,第10周时呈典型肾小球硬化,第13周时出现广泛的肾小球硬化和小管间质纤维化。随着模型组大鼠肾组织病理改变逐步加重及尿蛋白量逐渐增加,肾皮质WT-1蛋白的表达量逐渐减少,第4、7、10、13周分别较对照组下降24%、42%、56%、70%。结论足细胞相对密度及相对数量的减少与蛋白尿的严重程度成正比,并与肾纤维化的发展呈时间依赖性。Objective To dynamically observe number of podocytes in adriamycin-induced nephropathy by investigate the expression of WT-1, and to explore the role of podocytes in development of proteinuria and chronic renal fibrosis. Methods 36 SD rats were randomly divided into model group and normal control group, adriamycin-in- duced nephropathy was induced by tail intravenous injection of aclarubicin for two times. Renal tissue samples were collected at the 4th ,7th, 10th and 13th week respectively. The renal histology was observed with light microscope and electronic microscope, the amount of proteinuria was measured with BCA protein assay kit. The semiquantit ative Western blot and immunohistochemistry was used to detect the level of WT-1. Results The amounts of proteinuria in the adriamycin-induced nephropathy model group significantly increased at the end of the 4th week compared with the normal control group （P 〈 0. 01 ）. Focal segmental glomerulosclerosis was found in the renal tissue of the glomernloselerosis model group at the end of the 7 th week. and was typical in the end of the 10th week, at the end of 13th week glomeruloselerosis and tubulointerstitial fibrosis was extensive. With the development of proteinuria and renal fibrosis, the protein level of WT-1 in the nephropathy group was reduced by 24% ,42% ,56% and 70% respectively as low as those in the normal control group. Conclusion A relative decrease of the density and an absolute decrease in the numuber of podocytes is positively correlated with the amount of proteinuria, maybe play a key role in the genesis and development of Chronic renal fibrosis.

关 键 词：肾硬化症 多柔比星 蛋白尿 

分 类 号：R979.1[医药卫生—药品] R692.3[医药卫生—药学]